A photomicrodynamic system with a mechanical resonator monolithically integrated with laser diodes on gallium arsenide.

A cantilever resonant microbeam, laser diodes, and a photodiode have been fabricated on the surface of a gallium arsenide substrate. The microbeam is excited photothermally by light from a laser diode. The vibration is detected with a photodiode as the variation in light output caused by the difference in optical length between the microbeam and another laser diode. A high carrier-to-noise ratio (45 decibels) is achieved with a short (3 micrometers) external cavity length. Such a small distance allows a lensless system, which increases the ease of fabrication. This work could lead to applications in which photomicrodynamic systems are monolithically integrated on a gallium arsenide substrate with surface micromachining technology.

Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner.

Alternative splicing of cyclin D1 gene mRNA has recently been demonstrated. The novel transcript shows no splicing at the downstream exon 4 boundary and encodes a protein with an altered carboxyl-terminal domain that is a cyclin D1 variant; exon 5 is not included in the coding sequence which terminates downstream of exon 4. We here produced cells that exogenously express each form of cyclin D1 and analysed their cell cycle regulation. We found that (1) alternative splicing forms of cyclin D1 modulated entry into the cell cycle in an inverse manner; (2) both splicing forms suppressed cell growth; and (3) cells overexpressing form [a] were inhibited from entry into and completion of the S phase, although form [b]-expressing cells showed no reduction of G1- to S transition. We also found that overexpression of either cyclin D1 form upregulated Rb gene products, suggesting that this upregulation may be one of the causes of growth suppression in cyclin D1 overexpressing cells.

Spatiotemporal expression of C-CAM in the rat placenta.

We investigated the expression of the immunoglobulin superfamily cell adhesion molecule, C-CAM, in developing and mature rat placenta. By immunohistochemical staining at the light microscopic level, no C-CAM-expression was seen before Day 9 of gestation, when it appeared in the trophoblasts of ectoplacental cones. On Day 10.5, spongiotrophoblasts and invasive trophoblasts around the maternal vessels of the decidua basalis were stained positively. On Day 12.5, C-CAM was detected in the spongiotrophoblasts of the junctional layer, but labyrinth trophoblasts and secondary giant trophoblasts were not stained. On Day 17.5, C-CAM was found only in the labyrinth and lacunae of the junctional layer. At this stage, both the labyrinth cytotrophoblasts of the maternal blood vessels and the endothelial cells of the embryonic capillaries were strongly stained. Placental tissues from gestational Days 12.5 and 17.5 were analyzed by immunoelectron microscopy to determine the location of C-CAM at the subcellular level. On Day 12.5, positive staining of the spongiotrophoblasts was observed, mainly on surface membranes and microvilli between loosely associated cells. On Day 17.5, staining was found primarily on the microvilli of the maternal luminal surfaces of the labyrinth cytotrophoblasts, and both on the luminal surface and in the cytoplasm of endothelial cells of the embryonic vessels. RT-PCR analysis and Southern blotting of the PCR products revealed expression of mRNA species for both of the major isoforms, C-CAM1 and C-CAM2. Immunoblotting analysis of C-CAM isolated from 12.5-day and 14.5-day placentae showed that it appeared as a broad band with an apparent molecular mass of 110-170 kD. In summary, C-CAM was strongly expressed in a specific spatiotemporal pattern in trophoblasts actively involved in formation of the placental tissue, suggesting an important role in placental development. In the mature placenta, C-CAM expression was confined to the trophoblastic and endothelial cells lining the maternal and embryonic vessels, respectively, suggesting important functions in placental physiology.

Pharmacological differentiation of epithelium-derived relaxing factor from nitric oxide.

We examined the possibility that nitric oxide is one of the epithelium-derived relaxing factors in guinea pig airways. First we studied whether nitric oxide could relax isolated tracheal strips, and then we examined the effects of known inhibitors of endothelium-dependent relaxation (EDR) in the vascular system [hemoglobin, methylene blue, and NG-monomethyl-L-arginine (L-NMMA)] on epithelium-dependent relaxation (EpDR) induced by hyperosmotic stimuli in perfused whole tracheal preparations. Mannitol (160 mM in Krebs-Henseleit solution) applied to the epithelial surface was used as an osmotic stimulus to induce EpDR after carbachol-induced contraction (2 microM, serosal side). Nitric oxide produced concentration-dependent and complete relaxation of epithelium-denuded tracheal strips. Preincubation of the whole trachea with hemoglobin significantly inhibited osmotic-induced EpDR (P less than 0.05), but preincubation with methylene blue and L-NMMA did not. Hemoglobin introduced into the epithelial side after EpDR induced by hyperosmotic stimuli reversed relaxation, but methylene blue and L-NMMA did not. These results suggest that, although EpDR and vascular EDR have some pharmacological similarities and nitric oxide can relax airway smooth muscle, nitric oxide is not responsible for osmotic-induced EpDR.

Late acquired words in childhood are lost earlier in primary progressive aphasia.

The psycholinguistic nature of the dissolution of the mental lexicon in a primary progressive aphasic patient was investigated in light of the general regression hypothesis that language dissolution is the inverse of language acquisition. Four years after onset of the symptoms, the patient scored 60% correct on a picture naming test, exhibiting some effects of lexical and sublexical age-of-acquisition, but 7 years after onset, he scored only 15% correct. While even a weak form of the regression hypothesis is not fully supported, age-of-acquisition effects seem to be preserved throughout the course of the lexical dissolution. Some implications are briefly discussed for future research.

Two-year follow up on the protective value of dust masks against farmer's lung disease.

Some advocate moving away from the farm environment for farmers affected with farmer's lung disease (FLD), but most affected farmers still live on farms. In this study, we evaluated the practicality of dust masks and their effectiveness in prevention of FLD. The dust masks we chose were practically used and no new severe episodes of FLD developed in 20 of 21 farmers with FLD using the masks during a 2-year period. When the farmers took off the dust masks in a farming environmental provocation test, statistically significant reductions in FVC (mean 3.43 to 3.351, p < 0.01), DLco (mean 19.6 to 18.2 ml/torr/min, p < 0.01), and DL/VA (mean 5.1 to 4.8 (x10(-3)) 1/torr/min, p < 0.01) were observed several hours after exposure. These findings suggest that the dust masks were used practically during routine dairy farming and were effective in protection against FLD.

Clinical characteristics of idiopathic interstitial pneumonia (IIP) with bullae.

Multiple bullae have often been observed in the lungs of patients with idiopathic interstitial pneumonia (IIP). The etiology of bullae has been considered to be distinct from that of interstitial pneumonia and honeycomb lesions seen in IIP. The incidence of bullae was evaluated in 27 IIP patients (male; 23 cases, female; 4 cases) and clinical factors which are related to the development of bulla were analyzed. Of the 27 patients, 16 (59%) had bullae. All 16 were male smokers, and had higher smoking indices (p < 0.01) than patients without bullae. Eleven of the 16 IIP patients with bullae had clubbed fingers (69%, p < 0.05). Roentgenologically, cysts (75%, p < 0.05), low attenuation area (56%, p = 0.06), and honeycomb appearance (94%, p = 0.07) were observed more often in IIP patients with bullae. These results suggest that smoking habits may have a close relationship to the development of bullae seen in patients with IIP.

Bronchogenic cyst with high carbohydrate antigen 19-9 in the cyst fluid and the serum.

A mass of 8 cm in diameter was revealed in the right upper lung field of a 46-year-old female patient. The chest X-ray film taken one year previously revealed only a linear shadow in the same position, which was thought to be a vacant cyst. The levels of carbohydrate antigen (CA) 19-9 in cyst fluid and serum were elevated, at 410,000 and 130 U/ml, respectively. After surgical resection, serum CA19-9 returned to normal. Pathologically, the cyst wall was lined with bronchial epithelium with no evidence of malignancy. Immunohistochemical study revealed CA19-9 positivity in the bronchial epithelium of the cyst wall.

Smoking promotes insidious and chronic farmer's lung disease, and deteriorates the clinical outcome.

Although the prevalence of serum precipitating antibodies for farmer's lung disease (FLD) is lower in smokers than in nonsmokers and FLD predominates in nonsmokers, the affects of smoking on the clinical course of the disease is not known. We compared the clinical findings and the prognosis between 12 smokers (SM-FLD) and 31 non-smokers with FLD (NS-FLD). There was no difference in age, sex, working years on farm, clinical symptoms, laboratory findings, radiographic findings, between the two groups. However, for the type of onset on the first visit for FLD, "acute single episode" type was less common, and "recurrent" and "insidious onset" types were more common in SM-FLD than in NS-FLD (8.3 vs 58.1, 91.7 vs 41.9%, respectively, p < 0.05). Although working status and mask wearing status were not significantly different between the two groups after the diagnosis of FLD, patients with symptoms and/or radiographic abnormalities of FLD of more than 6 months were found more frequently in SM-FLD than in NS-FLD (66.7 vs 19.4%, p < 0.005). And also SM-FLD had more recurrences of FLD than NS-FLD after the initial diagnosis of FLD (1.58 +/- 1.56 vs 0.47 +/- 1.07, p < 0.05). SM-FLD tended to have lower % VC than NS-FLD (73.6 +/- 7.4 vs 88.5 +/- 3.9%, respectively, p = 0.06). Regarding the prognosis, the 10-year survival rates were 70.7% in SM-FLD, and 91.5% in NS-FLD (p < 0.05). These results suggest that smoking may make FLD insidious and chronic, and deteriorates the clinical outcome.

[Expression of HGF and c-met/HGF receptor mRNA in brains of normal rats and in phaeochromocytoma cells PC-12 of rats treated with NGF].

Gene expression of HGF and c-met proto-oncogene was examined during rat brain development and in cultured PC-12 cells, using reverse-transcriptase (RT)-polymerase chain reaction (PCR) technique. The both mRNAs of HGF and c-met proto-oncogene were remained at low levels in the middle and late stages of gestation (E-13 and E-18). After birth, and the level of both mRNA expression suddenly increased. During P-1 and P-12, their high level of expression continued and then decreased in P-20 and adult brain. Both HGF mRNA and c-met photo-oncogene mRNA were transiently expressed between day 2 and day 5, and disappeared in cultured PC-12 cells treated with NGF. The neurites of PC-12 cells that were treated with anti-sense oligonucleotides of HGF and c-met proto-oncogene, were shorter and fewer in number than untreated control cells. We conclude that neurite extension of PC-12 cells treated with NGF may ensue by way of c-MET protein activation and signal transduction pathways. Thus, c-MET protein activation and up-regulation of the two mRNAs may also play an important role in neuronal maturation in the developing rat brain.

[Up-regulation of NGF, trkA, Fas, down-regulation of bcl-2, and induction of apoptosis by propentofylline in human glioma cell lines].

Propentofylline (PPF) has been reported to stimulate the synthesis/secretion of nerve growth factor (NGF) by cultured mouse astroglial cells. In the present study, we examined whether PPF stimulates NGF synthesis in human glioma cell lines, the same as in mouse astroglial cells, and if so, whether NGF has a biological effect on glioma cells. After administration of PPF into the glioma cell lines, we investigated morphological changes and gene and protein expression of NGF, trkA, Fas and bcl-2 by using GFAP staining. Western blotting, and RT-PCR. Glioma cells showed definite morphological changes, including expansion of astrocytic processes, cytoplasmic enlargement and increases in GFAP staining. Interestingly, apoptosis was identified by DNA ladder formation in each of the cell lines. The mRNA and protein expression of NGF, trkA and Fas increased, but expression of bcl-2 decreased. These findings suggest that PPF works as a transcriptional modulator and induces apoptosis in glioma cells.

[Neural protective agents, propentofylline (PPF) could induce apoptotic cell death in the human glioma cells: analysis of Bcl-2 and Bax alpha/Bax beta expressions].

In the previous study, we have shown that propentofylline (PPF) could induce the cellular differentiation and apoptosis-related growth regression in the human glioma cell lines. Its biological functions were partly due to the increasing endogeneous NGF and its high affinity receptor, trk A productions. Although little has been known about the precise machinary regulating the propentofylline induced apoptosis. Recently, we have found that propentofylline could modulate some apoptosis related genes products in the glioma cell lines, i.e. NGF, trk A mRNA levels and Fas protein expressions were increased, whereas bcl-2 mRNA level was decreased. In the present study, we examined the apoptotic signal cascade, especially focusing on the expressing pattern of Bcl-2/Bax gene products. In the normal human astrocyte cells, Bax-beta was markedly expressed, whereas Bcl-2 and Bax-alpha proteins and mRNA were weakly or even nondetectable. Accordingly, Bax beta might be a dominant variant in the normal glial cells, which could have the appropriate balance of proapoptotic (Bax beta) and anti-apoptotic proteins (Bcl-2). In the glioma cells, we showed the over-expressions of Bcl-2 and Bax alpha compared with the normal counterparts. According to Bax dominant theory, Bax, not Bcl-2 may have a major role in regulating apoptosis by means of homodimerization. In might be implied that in the glioma cells, excessive expressions of Bcl-2 and Bax alpha would favor the formation of the Bax alpha/Bax beta heterodimer or the Bax beta/Bcl-2 heterodimer rather than the Bax beta/Bax beta homodimer, which might be presumed to be functional proteins. And finally the increasing relative ratio of Bax alpha/ Bax beta or Bax beta/Bcl-2 to Bax beta/Bax beta could allow the tumor cells to survive. Thus over-expression of the bcl-2 and bax alpha gene renders the glioma cells resistant to apoptosis. In the present study, PPF could promote Bax beta over-expression and Bcl-2 retardative expression in the glioma cells, whereas had no effect on Bax alpha expression. Therefore, PPF might promote apoptotic cell death through the mechanism that restore the glioma cells to the appropriate balance of proapoptotic and anti-apoptotic proteins like as normal astrocytes. Our results indicated that propentofylline might have a potential role as apoptotic modulators in the human glioma cell lines, not only its protective activities against neuronal ischemic damages.

[Induction of apoptosis through NGF/p75NTR in human glioma cells treated with propentofylline].

Propentofylline (PPF) is a xanthine derivative and it has been reported that PPF stimulated the synthesis/secretion of nerve growth factor (NGF) by cultured astroglial cells. We have reported that PPF induced apoptosis in human glioma cells and as its mechanism, up-regulation of NGF, Fas, Bax beta and down-regulation of Bcl-2 were assumed. Recent studies demonstrated the presence of apoptosis induced via NGF/p75NTR in developmental neuron, oligodendroglia. In the present study, to examine whether signal cascade via NGF/p75NTR participates the apoptosis in human glioma cells treated with PPF, we investigated the immunohistochemical study using anti-mouse monoclonal antibody, immunoprecipitation and northern blot analysis for p75NTR, NF-kappa B in human glioma cells (U251MG, T98G, U87) treated with PPF. We observed the up-regulation of p75NTR, translocation of NF-kappa B to the nucleus after treatment with PPF in these cell lines. According to above results, it is assumed that apoptosis in human glioma cells treated with PPF was induced via NGF/p75NTR.

[Three adults with mild varicella and bronchial mucosal lesions].

We encountered three adults with varicella and bronchial mucosal lesions. Respiratory symptoms were minimal in all three. Chest X-ray films showed bilateral, diffuse, small, nodular shadows. Small, elevated lesions with white plaque's were seen on the bronchial mucosa bronchoscopically. Transbronchial lung biopsy, bronchial mucosal biopsy, and bronchoalveolar lavage were also done. The lung-biopsy specimen showed infiltration of lymphocytes into the interstitial space: VZV antigen was found by immunohistochemical staining of the lesion in one case. Analysis of bronchoalveolar lavage fluid revealed abnormally low CD 4/8 ratios in three cases. These findings suggest a high incidence of respiratory complications, especially bronchial lesions, despite the lack of respiratory symptoms, in adults with varicella.

[Surgical treatment of inflammatory abdominal aortic aneurysm].

A 53-year-old man was hospitalized with chronic abdominal pain. A CT scan was performed and demonstrated an aortic aneurysm surrounded by a soft tissue mantle. In the laparotomy, extensive fibrotic adhesions between the aneurysm and the duodenum were discovered. This made mobilization of the duodenum and the left renal vein difficult. The aortic wall was white, thickened, and surrounded with dense fibrous tissue. The aneurysm was replaced by a Dacron graft. Histology of the fibrous tissue showed the features of chronic inflammation. He had no abdominal pain after the operation, and he was discharged in good health. In the preoperative diagnosis of inflammatory aneurysms, the CT scan is useful. We are of the opinion that the preferred treatment for inflammatory aneurysm is aneurysmectomy (or aneurysmorrhaphy) plus grafting.

Ion beam sputtered (SiO(2))(x)(Si(3)N(4))(1-x) antireflection coatings on laser facets produced using O(2)-N(2) discharges.

The chemical composition of a (SiO(2))(x)(Si(3)N(4))(1-x) film produced by ion beam sputtering was precisely controlled by the ratio of O(2) and N(2) flow rates under a discharge current kept constant to within an accuracy of +/-0.05 A. The reproducibility of the refractive index was improved to +/-0.01. This film was applied to form antireflection coatings with extremely low reflectivity on facets of 830-nm AlGaAs double heterostructure lasers. The minimum reflectivity was 6.8 x 10(-5), and a reflectivity of 1 x 10(-4) was achieved reproducibly. Experimental studies show that antireflection coatings are effective for suppressing the interferometric light output variation of composite cavity lasers.

Imaging in primary progressive aphasia.

Primary progressive aphasia (PPA) presents with aphasia, with or without other minor cognitive dysfunction. We report five patients with PPA to show the correlation between their clinical signs and imaging findings. The patients can be divided into those with nonfluent (group 1) and those with fluent (group 2) aphasia. The characteristic speech impairment was bradylalia in group 1 and word amnesia in group 2. Impairment of comprehension was common but mild in both groups. On MRI, patients in group 1 showed predominantly left frontal and perisylvian atrophy with reduced uptake in the same region on single photon emission computed tomography (SPECT) using technetium-99m hexamethyl propyleneamine oxime (99mTc HMPAO). Patients in group 2 showed left temporal atrophy involving the superior, middle and inferior temporal gyri, hippocampus and parahippocampal gyrus on MRI and reduced uptake in the same region on SPECT. These findings correlated well with the functional anatomy of speech impairment.

Applications of an extremely short strong-feedback configuration of an external-cavity laser diode system fabricated with GaAs-based integration technology.

A composite-cavity laser diode is used to monitor the reflectivity or the displacement of the external-cavity mirror for micromechanical photonics devices. Optical disk bits are read out in the near field from the difference in medium reflectivity with an antireflection-coated laser diode and a photodiode. Microbeam vibration is also detected in the near field from the phase difference with an uncoated laser diode and a photodiode. In both cases the carrier-to-noise ratio is very high (more than 45 dB) because of the lack of mode-hopping noise resulting from the extremely short (less than 3 µm) external-cavity length and strong light feedback. These composite-cavity laser diode microdevices are fabricated on a gallium arsenide substrate to eliminate the need for optical alignment.

Optical trapping of low-refractive-index microfabricated objects using radiation pressure exerted on their inner walls.

Optical trapping of transparent ring-shaped micrometer-sized objects with a refractive index lower than that of the surrounding medium has been demonstrated by use of a strongly focused TEM(00)-mode laser beam. Axial trapping of these objects is a result of the upward radiation pressure induced when the incident light strikes the inner wall and transmitted light leaves from the bottom. Transverse trapping of these objects occurs because the total repulsive radiation pressure exerted on the inner wall of the object is directed toward the laser beam axis. Three-dimensional manipulation of f luorinated polyimide micro-objects (refractive index n(1)= 1.525, outer diameter 10 microm, inner diameter 5 microm, and thickness 5.7 microm) in a high-refractive-index liquid (n(2)= 1.605) was experimentally shown to be possible by use of an objective lens with a wide range of numerical apertures from 1.25 to 0.5.

Supersmall flying optical head for phase change recording media.

A supersmall optically switched laser (OSL) head is proposed. A laser diode attached to an air bearing slider forms a complex cavity together with a recording medium, and its light output is detected by a photodetector placed at the other end of the laser facet. Data signals and track error signals read from the sampled servo marks are successfully detected. The signal amplitude variation caused by the flying height change is much reduced, and the SNR is increased to 36 dB (40 kHz to 20 MHz for a phase change medium) by decreasing the reflectivity of the laser facet facing the medium to <5%.